title: A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.
abstract: OBJECTIVE
  Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types.
  
  
  METHODS
  Samples were available from 157 T2-T4 laryngeal cancer and 185 T1-T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide (ARCON) and bladder carbogen nicotinamide (BCON) phase III randomized trials of radiotherapy alone or with carbogen and nicotinamide (CON) respectively. Customized TaqMan low density arrays (TLDA) were used to assess expression of the 26-gene signature using quantitative real-time PCR. The median expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low (≤median) or TLDA-HS high (>median). The primary outcome measures were regional control (RC; ARCON) and overall survival (BCON).
  
  
  RESULTS
  Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors. Five-year RC was 81% (radiotherapy alone) versus 100% (CON) for TLDA-HS high (P=0.009). For TLDA-HS low, 5-year RC was 91% (radiotherapy alone) versus 90% (CON; P=0.90). TLDA-HS did not predict benefit from CON in bladder cancer.
  
  
  CONCLUSIONS
  The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer. These findings will be evaluated in a prospective clinical trial.
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Christie Hospital, Manchester, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Eustace
authors.forename: Navin
authors.initials: N
authors.lastname: Mani
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Joely J
authors.initials: JJ
authors.lastname: Irlam
authors.forename: Janet
authors.initials: J
authors.lastname: Taylor
authors.forename: Guy N J
authors.initials: GN
authors.lastname: Betts
authors.forename: Helen
authors.initials: H
authors.lastname: Denley
authors.forename: Crispin J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Jarrod J
authors.initials: JJ
authors.lastname: Homer
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rojas
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hoskin
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Buffa
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
mesh_terms: D002245:Carbon Dioxide / Q000008:administration & dosage; D015687:Cell Hypoxia / Q000235:genetics* / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage; D010100:Oxygen / Q000008:administration & dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen